Chirality of the molecular assembly determined by intra-/inter-N- Ha?O hydrogen bonding in doubly substituted N-octanoylglyoxylic amides

Article abstract of DOI:10.1016/j.tet.2013.07.052

N-Octanoylglyoxylic amides have been synthesized from N-octanoylisatins and their self-assembly analyzed in the solid state by X-ray crystallography. Of the seven compounds, only two utilize intramolecular N1-H1a?O2 hydrogen bonds, whereas five of them fo

Full text of DOI:10.1016/j.tet.2013.07.052

Tetrahedron 69 (2013) 8446e8455
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Chirality of the molecular assembly determined by
intra-/inter-NeH/O hydrogen bonding in doubly
substituted N-octanoylglyoxylic amides
,
Venty Suryanti a y, Mohan Bhadbhade b, Roger Bishop a, David StC. Black a,
,
Naresh Kumar a
*
a School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
b Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
N-Octanoylglyoxylic amides have been synthesized from N-octanoylisatins and their self-assembly an-
alyzed in the solid state by X-ray crystallography. Of the seven compounds, only two utilize intra-
molecular N1eH1/O2 hydrogen bonds, whereas five of them forgo this intramolecular hydrogen bond
to achieve two centrosymmetric NeH/O bonds possessing a non-planar conformation with intra-
molecular triple C]O/C]O dipolar contacts. These alternative conformations with resulting in-
termolecular interactions influence the self-assembly process distinctly; the former have molecules
packed in chiral space groups whereas the latter associate in non-chiral space groups.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 18 April 2013
Received in revised form 3 July 2013
Accepted 15 July 2013
Available online 20 July 2013
Keywords:
Glyoxylamides
N-Acylisatins
Assembly
Peptidomimetics
1. Introduction
donor properties and a comparatively high molecular dipole mo-
ment. These properties allow glyoxylamides to establish highly
Investigation of hydrogen bonding patterns and other forms of
inter- and intramolecular interactions are of profound interest due
to their potential applications in molecular recognition, crystal
engineering and biological and material sciences.1 In particular, the
hydrogen bond motifs of carboxylic acids and amides have been
particularly well studied and are well-known to form reliable su-
pramolecular synthons.2,3 Such self-assembled structures can be
formed by a variety of building blocks, where peptides have drawn
significant attention due to their structural diversity. The applica-
tion of peptide building blocks in biosensors, tissue engineering
and the development of antibacterial agents has also already been
demonstrated.4 However, designing synthetic self-assembled ar-
chitectures formed by amphiphilic molecules to construct func-
tional materials remains a big challenge.5
variable tectons for the construction of supramolecular
assemblies.6e8 Despite this, these interesting molecules have been
poorly studied to date.
In previous studies, we found methyl 2-(2-(2-acetamidophenyl)-
2-oxoacetamido)acetate 1 self-assembles into a dimer via hydrogen
bonding between the glyoxylamide NH proton and the acetamide
oxygen atom.9 Introduction of an alkyl chain on the glyoxylamide to
give N-acetylglyoxylic amides 2aec and 3 was found to further en-
hance the self-assembly properties of these compounds, which no
longer favoured the dimeric conformation displayed by the parent
compound 1. Different molecular conformations were observed for
compounds 2aec and 3, arising from different cooperative effects
between strong and weak interactions.10
In order to better understand the self-assembly properties of
amphiphilic glyoxylamides and to construct unique supramolec-
ular assemblies, it was of interest to subsequently examine the
self-assembly of a new series of N-acylglyoxylic amides, which
bear a hydrophobic alkyl chain on the amide side of the molecule
or long alkyl chains on both sides of the molecule. Herein, we
report the supramolecular architectures as a result of intra/in-
termolecular interactions displayed by these new N-octanoyl-
glyoxylic amides 4.
The structures of corresponding glyoxylamides possess re-
markable molecular features, such as hydrogen bond acceptor/
* Corresponding author. Tel.: þ61 2 9385 4698; fax: þ61 2 9385 6141; e-mail
address: n.kumar@unsw.edu.au (N. Kumar).
y
Present address: Department of Chemistry, The University of Sebelas Maret,
Surakarta, Jawa Tengah 57126, Indonesia.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.052

V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
8447
Table 1
Synthesis of N-octanoylglyoxylic amides 7
Entry
Product
R1
R2
Yielda (%)
1
5
3
4
5
6
7
8
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
H
Br
CH3
H
Br
CH3
H
Br
CH3
H
Br
H
H
H
CH3
CH3
CH3
(CH2)5CH3
(CH2)5CH3
(CH2)5CH3
(CH2)11CH3
(CH2)11CH3
(CH2)11CH3
(CH2)17CH3
(CH2)17CH3
(CH2)17CH3
63
72
60
67
56
71
71
64
73
60
67
66
59
55
56
9
10
11
12
13
14
15
CH3
H
Br
CH3
a
Isolated yield (reaction was not optimized).
2. Results and discussion
2.1. Synthesis of N-octanoylglyoxylic amides
N-Octanoylisatins 6aec were prepared by addition of the isatin
5aec to a suspension of sodium hydride in dry THF, followed by
dropwise addition of octanoyl chloride in dry THF to the purple
mixtures at 5 ꢀC. The reaction mixtures were subsequently warmed
to room temperature and then quenched with ice water and
extracted with ethyl acetate to give N-octanoylisatins 6 in 78e87%
yields (Scheme 1).
Scheme 2. Reagents and conditions: amino acid alkyl ester hydrochloride salt,
NaHCO3, CH2Cl2/H2O (1:1 v/v), 0 ꢀC to rt, 24 h.
Table 2
Synthesis of N-octanoylglyoxylic amide peptidomimetics 9
Entry
Amino acida
Product
R1
R2
Yieldb (%)
1
2
3
4
5
6
Glycine
9a
9b
9c
9e
9d
9f
H
CH3
H
CH3
H
CH3
CH3
CH3
(CH2)3CH3
(CH2)3CH3
(CH2)5CH3
(CH2)5CH3
46
52
44
56
42
55
L
-Alanine
Glycine
-Alanine
Glycine
-Alanine
L
L
a
As the alkyl ester hydrochloric salt.
Isolated yield (reaction was not optimized).
b
Scheme 1. Reagents and conditions: (i) octanoyl chloride, NaH, THF, 0 ꢀC to rt, 4 h,
(ii) amine, CH2Cl2, reflux, 4 h.
temperature. Crystals suitable for X-ray structure determination
were successfully obtained for compounds 7a, 7d, 7i, 7k, 7l, 9a and
9d, while the other compounds afforded only amorphous solids.
N-Octanoylisatins 6 were then subjected to nucleophilic ring-
opening with a range of amines and amino acid alkyl esters.
Treatment of N-octanoylisatins 6 with ammonia or methylamine in
dichloromethane under reflux for 1e2 h gave the corresponding N-
octanoylglyoxylic amides 7aef in 56e72% yields. Similarly, reaction
of N-octanoylisatins 6 with hexylamine, dodecylamine or octade-
cylamine under reflux in dichloromethane for 4e6 h generated the
corresponding N-octanoylglyoxylic amides 7geo in moderate to
good yields of 55e71% (Scheme 1, Table 1).
The corresponding N-octanoylglyoxylamide amino acid de-
rivatives 9 were prepared via our previous described methods.11
The N-octanoylisatin 6a was stirred in dichloromethane for
24e28 h with an amino acid methyl ester hydrochloride salt 8 and
sodium hydrogen carbonate, initially at 5 ꢀC and then gradually
warmed to room temperature to give the desired glyoxylamide
peptidomimetics 9a,b in 44e52% yields. In a similar fashion,
treatment of N-octanoylisatin 6a with a variety of amino acid alkyl
ester hydrochloride salts 8 produced the corresponding glyox-
ylamide peptidomimetics 9cef in 42e56% yield (Scheme 2,
Table 2).
2.2. Crystal structures
Single crystal X-ray structure determinations were carried out
on compounds 7a, 7d, 7i, 7k, 7l, 9a and 9d. A summary of their
crystallographic data is provided in Table 3. Crystal structures of
these compounds have well ordered alkyl chains, but 7a contained
two crystallographically independent molecules, one with an or-
dered structure and one disordered with two alternate conforma-
tions. The bromo compound 7k was isostructural with the methyl
compound 7l.
It is intriguing to note that only two of the molecules (7a and 9d)
utilize intramolecular N1eH1/O2 hydrogen bonding, whereas the
remaining five (7d, 7i, 7k, 7l and 9a) adopt different conformations
to achieve stabilization through C]O/C]O dipolar contacts in-
volving three C]O groups (the two carbonyls of the glyoxylamide
and the amide carbonyl group). However, the reasons that in-
fluence these alternatives are not obvious. Fig. 1 shows the crystal
structures of 9a and 9b depicting the significant intramolecular
interactions. Crystal structures of 7a, 7d, 7i, 7k and 7l are shown in
Fig. S1, Supplementary data. These two choices of conformations,
either to form NeH/O or C]O/C]O contacts, are achieved by
Glyoxylamides 7 and 9 were subsequently recrystallized from
a range of solvents including methanol, ethanol, dichloromethane/
hexane and acetonitrile via slow evaporation of the solvent at room

8448
V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
Table 3
Crystal data collection and structure refinement parameters of 7a, 7d, 7i, 7k, 7l, 9a and 9d
Compound
7a
7d
7i
7k
7l
9a
9d
Chemical formula
Mr
C16H22N2O3
580.71
C17H24N2O3
304.38
C23H36N2O3
388.54
C28H45BrN2O3
537.57
C29H48N2O3
472.69
C19H26N2O5
362.42
C30H20N4O6
532.50
Crystal system
Space group
Temperature (K)
Orthorhombic
P212121
152
7.8980 (7),
9.8793 (9),
39.517 (4)
d
Orthorhombic
Pbca
100
9.906 (2),
17.958 (4),
19.396 (4)
d
Orthorhombic
Pbca
100
14.005 (3),
9.4400 (19),
35.398 (7)
d
Orthorhombic
Pca21
154
13.7253 (17),
22.889 (3),
9.3591 (11)
d
Orthorhombic
Pca21
154
13.7253 (17),
22.889 (3),
9.3591 (11)
d
Triclinic
Monoclinic
P21
100
5.096 (1), 42.589 (9),
5.4520 (11)
Pꢁ1
155
ꢀ
a, b, c (A)
8.8866 (7),
9.9456 (11),
12.5215 (15)
76.528 (5),
85.606 (5),
63.657 (3)
964.01 (17)
2
a,
b
,
g
(ꢀ)
90, 98.40 (3), 90
3
ꢀ
V (A )
3083.4 (5)
4
0.09
3450.4 (12)
8
0.08
4679.9 (16)
8
0.07
2940.2 (6)
4
1.43
2940.2 (6)
4
0.07
1170.6 (4)
2
0.07
Z
m
(mmꢁ1
)
0.09
Crystal size (mm)
Tmin, Tmax
0.60ꢂ0.33ꢂ0.05
0.03ꢂ0.02ꢂ0.01
Absorption
corrections
are not applied
36,556, 2543,
2388
0.10ꢂ0.02ꢂ0.01
Absorption
corrections
are not applied
41,308, 3863,
2892
0.50ꢂ0.10ꢂ0.02
0.51ꢂ0.32ꢂ0.04
0.34ꢂ0.11ꢂ0.08
0.10ꢂ0.02ꢂ0.01
Absorption corrections
are not applied
0.950, 0.996
0.538, 0.967
0.966, 0.997
0.970, 0.993
No. of measured,
independent
18,504, 5294,
3459
17,744, 4661,
2079
17,993, 4926,
3325
12,366, 3335,
2381
14,483, 3773, 3655
and observed
[I>2
reflections
Rint
R[F2>2
s(I)]
0.098
0.147, 0.347,
1.20
0.024
0.042, 0.112,
1.09
0.099
0.081, 0.185,
1.12
0.139
0.075, 0.233,
1.06
0.086
0.065, 0.192,
1.07
0.037
0.038, 0.128,
1.03
0.233
0.075, 0.168, 0.90
s
(F2)], wR(F2), S
No. of reflections
No. of parameters
No. of restraints
5294
376
414
2543
201
0
3863
260
0
4661
309
53
4926
320
79
3335
241
0
3773
282
1
ꢀꢁ3
imin (e A
D
imax
,
D
)
0.58, ꢁ0.75
0.29, ꢁ0.24
0.25, ꢁ0.33
0.43, ꢁ0.80
0.42, ꢁ0.36
0.29, ꢁ0.37
0.54, ꢁ0.44
CCDC number
915508
915509
915510
915511
915512
915513
915514
O interactions with the amide carbonyl group. This triple carbonyl
interaction was observed in two crystal structures formed by 2c and
reported in our earlier paper.10 The intercarbonyl distances
ꢀ
ꢀ
(2.52e3.15 A) and angles (74e123 ) for these structures appear in
Table S1, Supplementary data. Allen et al. have described both the
antiparallel and orthogonal C]O/C]O dipolar interactions.13 The
orthogonal motif is encountered more frequently, especially in
crystal structures of proteins and other amide-containing com-
pounds,14,15 because it is less subjected to steric effects.16 However,
the intramolecular orthogonal triple carbonyl dipolar association is
the variant observed here. Although the distances observed are
conventional, several of the angles are slightly compromised by the
molecular geometry and deviate from ideal orthogonality. None-
theless, this packing motif occurs consistently and it is clearly ef-
fective for molecules of this general type. Although Allen et al.
demonstrated that these dipolar interactions can compete effec-
tively with strong hydrogen bonds in crystal packing,13 the situa-
tion is rather different here since the carbonyl dipoles operate
together with strong and weak hydrogen bonding interactions
(NeH/O and CeH/O).
Fig. 1. Intramolecular interactions present in molecules 9a (left) and 9d (right). Black
dotted lines represent the hydrogen bonding interactions, whereas the blue dotted
lines represent the dipolar C]O/C]O interactions.
2.3. Supramolecular organization
rotating both the side chains about the C1eN1 and C2eC8 bonds by
approximately 180ꢀ, respectively. The NeH/O hydrogen bonding
keeps the aromatic ‘head’ part co-planar with the amide group at
C2 and the glyoxylamide at C3, whereas in making the dipolar
contacts these groups deviate out of plane. The resulting effects on
their supramolecular organization are discussed later. The geo-
metric parameters of the intramolecular interactions are given in
Table S1, Supplementary data.
The amide and glyoxylamide chains interact with each other in
the five crystal structures (7d, 7i, 7k, 7l and 9a) for which the
N1eH1/O2]C intramolecular hydrogen bond is absent. The two
carbonyls of the glyoxylamide functionality adopt their normal
transoid conformation12 and both participate in dipolar C]O/C]
Interesting correlations were observed between intramolecular
contacts and their effect on the overall molecular organization.
When the molecule makes intramolecular C]O/C]O contacts,
both NeH groups form intermolecular NeH/O hydrogen bonds,
which are always across a centre of symmetry. However, when N1
makes an intramolecular N1eH1/O2 hydrogen bond, this leaves
only N2 available for the intermolecular NeH/O contact, which is
repeated by translation along the shortest unit cell axis. The in-
termolecular interaction distances and angles of all seven struc-
tures are summarized in Table S2, Supplementary data.
The five crystal structures (7d, 7i, 7k, 7l and 9a) that feature the
intramolecular triple carbonyl interaction motif also contain sig-
nificant intermolecular NeH/O]C hydrogen bonded associations.

V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
8449
Molecules of 9a (Fig. 2) are arranged along the b direction and their
interaction results in the formation of tape assemblies.17,18 Two
cyclic centrosymmetric hydrogen bonded motifs are present, in-
volving eCOeCOeNH/O]CeNHe interaction on one side of the
molecule, and eCOe(NH)C]O/HNeCOe interaction on the other.
Similar arrangements are present in the other four crystal struc-
tures, and all five form non-chiral space groups.
Fig. 4. Crystal structure of 7a showing how the two crystallographically independent
molecules (green or blue) form a hydrogen bonded tape assembly.
inspection reveals a tape running along the direction of the ab di-
agonal.19,20 This is created by two molecules of 7a in adjacent di-
mers interacting by means of /HeNeC]O/ hydrogen bonding to
produce an eight-membered cycle around a second pseudo-
inversion centre.
Fig. 2. Crystal structure of 9a, highlighting the intermolecular amide hydrogen
bonding along b.
The chloroemethyl interchange rule is an unusual phenomenon
encountered in crystal engineering. If only molecular close packing
is significant, then the similar spherical shape and size of chloro
The remaining crystals (7a and 9d) contain intramolecular
H1eN1/O2 hydrogen bonding, but also utilize intermolecular
amide hydrogen bonding. These crystals are more complex, in the
sense that their achiral molecules assemble to produce helices and
these cause formation of the chiral space groups P212121 and P21,
respectively. In the case of 9d, the molecules are simply translated
along a and are linked into a hydrogen bonded chain by means of
eCOe(NH)C]O/HNeCOeCOe interactions (Fig. 3).
3
ꢀ
3
ꢀ
(20 A ) and methyl (24 A ) groups can allow two isosteric mole-
cules to adopt the same crystal packing.20e22 On the other hand,
since chlorine has a rich interaction chemistry that differs consid-
erably from methyl, entirely different crystal structures will result
in other cases. If the chlorine atom is involved in significant in-
teractions within its crystal, e.g., a structure containing Cl/Cl as-
ꢀ
sociations of less than 4 A, then it is unlikely that crystals of its
methyl analogue will pack in the same manner. The occurrence of
chloroemethyl isostructurality has been estimated to be around
26%.23 Here, bromo compound 7k and methyl compound 7l crys-
tallize in the same manner, making this an example of the less
commonly reported bromo-methyl interchange. The bromine atom
3
ꢀ
(26 A ) of 7k does not participate in any major intermolecular at-
tractions, its closest contact being with two hydrogen atoms of
ꢀ
ꢀ
ꢀ
a neighbouring methyl group (d¼3.281 A and 3.355 A; D¼3.615 A).
The isostructural methyl compound 7l has a corresponding C/C
ꢀ
value of D¼3.685 A.
The van der Waals interactions between alkyl chains
(alkyl/alkyl chains at w4 A) was observed predominantly in
ꢀ
structures 7a and 9d (Fig. 5), containing intra NeH/O hydrogen
bonding. Similar packing motifs were also noted in structures
containing longer alkyl chains (2a, 2b and 3).10 The remaining five
structures (7d, 7i, 7k, 7l and 9a) lacking the intramolecular
NeH/O hydrogen bond contained packing modes that lacked this
alkyl/alkyl chain interaction. Crystal packings of 9a and 9b are
shown in Fig. 4 and crystal packings of 7a, 7d, 7i and 7l are shown in
Fig. S2, Supplementary data.
Fig. 3. Crystal structure of 9d showing the intermolecular hydrogen bonded chain. The
21 screw axis (not shown) runs along the (horizontal) long axis b.
The intermolecular hydrogen bonding behaviour of the glyox-
ylamides in the solid state were also obtained from FT-IR spec-
troscopy by focussing on the three amide vibrations, NeH
Crystals of 7a contain two crystallographically independent
molecules (coloured green and blue in Fig. 4). These form a dimeric
stretching (nNeH), C]O stretching (amide I) and NeH bending
assembly around
a
pseudo-inversion centre by using in-
(amide II). Characteristic intermolecular hydrogen bonding IR
termolecular NeH/O]C hydrogen bonds. Further association of
bands24e26 were observed for 7aeo and 9aef at 3406e3172 cmꢁ1
these dimers looks at first like a ladder assembly,19 but closer
(n
NeH), 1658e1597 cmꢁ1 (amide I) and 1544e1512 cmꢁ1 (amide

8450
V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
spectra were recorded with a Thermo Nicolet 370 FTIR spectrom-
eter with the sample prepared as a KBr pellet. UVevis spectra were
recorded using a Varian Cary 100 Scan spectrometer. NMR data
were recorded using a Bruker DPX300 instrument (1H 300 MHz, 13
C
75.4 MHz) at 25 ꢀC and reported as chemical shift (
d) relative to
SiMe4. Low and high resolution mass spectrometric analysis was
carried out at the Biomedical Mass Spectrometry Facility, UNSW
and the spectra was recorded on Q-TOF Ultima API (Micromass).
Microanalyses were performed on a Carlo Erba Elemental Analyzer
EA 1108 at the Campbell Microanalytical Laboratory, University of
Otago, New Zealand. Gravity column chromatography was carried
out using Merck 230e400 mesh ASTM silica gel.
4.1.1. 1-Octanoylindoline-2,3-dione 6a. A mixture of octanoic acid
(10.88 g, 61.5 mmol) and excess thionyl chloride was heated at
reflux for 2 h, and then N2 gas was introduced to remove the
remaining thionyl chloride to give the octanoyl chloride. To a sus-
pension of sodium hydride (1.30 g, 54 mmol) in dry THF (80 mL)
was added isatin (6.02 g, 41 mmol) in small portions over 15 min
under nitrogen. Octanoyl chloride in dry THF (20 mL) was then
added dropwise to the chilled purple mixture over 5e10 min. The
reaction mixture was warmed to room temperature for 4 h. The
reaction mixture was then carefully quenched with ice water and
extracted with ethyl acetate. The combined organic extracts were
washed with water, dried over anhydrous sodium sulfate, filtered
and concentrated under reduced pressure. The crude material was
recrystallized from hexane to give the compound as a brownish
yellow solid (9.29 g, 83%). Mp 82e84 ꢀC; 1H NMR (300 MHz, CDCl3):
Fig. 5. Crystal packings of 9a (left) and 9d (right).
II), indicating that these glyoxylamide series were highly packed
with hydrogen-bonded amides.
The concentration-dependent 1H NMR spectroscopy measure-
ments of NH groups-containing compounds show the presence of
intermolecular NH hydrogen bonding interactions for their aggre-
gation in solution.27e31 Intermolecular
pep stacking interactions
also have been demonstrated to play a fundamental role in stabi-
lizing the self-assembled supramolecular structures of aromatic
ring-containing compounds.32e35 In these glyoxylamide series
having NH groups and aromatic ring, the intermolecular NH hy-
drogen bondings and pep stacking interactions are expected to be
the driving forces for aggregation to persist in the solution phase.
d
0.89 (t, J¼6.5 Hz, 3H, CH2(CH2)5CH3), 1.25e1.46 (m, 8H,
CH2CH2(CH2)4CH3), 1.70e1.79 (m, 2H, CH2CH2(CH2)4CH3), 3.10 (t,
J¼7.3 Hz, 2H, CH2CH2(CH2)4CH3), 7.33 (dt, J¼7.5, 0.9 Hz, 1H, ArH),
7.69e7.79 (m, 2H, ArH), 7.89 (dd, J¼8.2, 0.5 Hz, 1H, ArH); 13C NMR
(75 MHz, CDCl3):
d 14.0 (CH2(CH2)5CH3), 22.5, 24.0, 28.9, 31.6
(CH2(CH2)5CH3), 38.3 (COCH2(CH2)5CH3), 118.3, 119.2, 125.2, 126.0
(ArCH), 138.8, 148.8 (ArC), 157.7, 173.1, 180.3 (C]O); IR (KBr): nmax
2955, 2918, 2852, 1749, 1656, 1592, 1579, 1335, 1465, 1384, 1356,
1330, 1277, 1259, 1204, 1131, 1087, 955, 886, 816, 759 cmꢁ1; UV
3. Conclusion
(DMF): lmax 238 (ε 2250 cmꢁ1
M
ꢁ1), 241 (2350), 261 (2850), 269
A series of N-octanoylglyoxylic amides were synthesized by
ring-opening of N-octanoylisatins with a range of amines and
amino acid alkyl esters. There are two types of molecular confor-
mations, which had a fundamental effect on the intermolecular
interactions used in the self-assembly process and the formation of
well-defined supramolecular architectures.
The five crystal structures (7d, 7i, 7k, 7l and 9a) that feature
triple C]O/C]O dipolar contacts have strong amide hydrogen
bonding along the b direction. Their molecular interactions resulted
in the formation of tape assemblies, which formed in non-chiral
space groups, e.g., Pbca, Pca21 and Pꢁ1.
(3750); HRMS (ESI) m/z calculated for C16H20NO3 (MþH)þ 274.1365.
Found 274.1429.
4.1.2. 5-Bromo-1-octanoylindoline-2,3-dione 6b. This compound
was prepared by the same method as compound 6a from 5-
bromoisatin (6.01 g, 27 mmol) and octanoyl chloride (6.59 g,
40.51 mmol) as a brownish yellow solid (7.39 g, 78%). Mp
142e144 ꢀC; UV (DMF): lmax 238 (ε 5550 cmꢁ1
M
ꢁ1), 252 (5700),
276 (7150); IR (KBr): nmax 2950, 2921, 2867, 1781, 1703, 1604, 1518,
1460, 1431, 1394, 1383, 1328, 1307, 1283, 1253, 1220, 1197, 1059, 972,
847, 770 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
0.88 (t, J¼6.6 Hz, 3H,
The crystals of 7a and 9d made both intra- and inter NeH/O
hydrogen bonds (only with translated molecules) interactions. The
planar head groups assembled to generate helices forming the
chiral space groups P212121 and P21, respectively. It is interesting
that a smaller amide exhibits dimorphic behaviour, one containing
intra NeH/O and the other one lacking it.36,37 Here, the synthe-
sized molecules with longer alkyl substituents have not shown any
polymorphic behaviour despite our thorough crystal screening.
Studies of the substituted glyoxylamides are still ongoing in order
to fully elucidate the factors, which control their self-assembly
process in the solid state.
CH2(CH2)5CH3),1.24e1.48 (m, 8H, CH2CH2(CH2)4CH3), 1.69e1.77 (m,
2H, CH2CH2(CH2)4CH3), 3.09 (t, J¼6.6 Hz, 2H, CH2CH2(CH2)4CH3),
7.82 (dd, J¼8.8, 2.2 Hz, 1H, ArH), 7.89 (dd, J¼2.2, 0.4 Hz, 1H, ArH),
8.37 (dd, J¼8.8, 0.4 Hz, 1H, ArH); 13C NMR (75 MHz, CDCl3):
d 14.1
(CH2(CH2)5CH3), 22.6, 24.1, 29.0, 29.0, 31.7 (CH2(CH2)5CH3), 38.3
(COCH2(CH2)5CH3), 119.5, 127.9, 136.1 (ArCH), 120.1, 141.3, 147.6
(ArC), 158.0, 173.1, 180.4 (C]O); HRMS (ESI) m/z calculated for
C16H19BrNO3 (MþH)þ 352.0543 (79Br). Found 352.0538 (79Br).
4.1.3. 5-Methyl-1-octanoylindoline-2,3-dione 6c. This compound
was prepared by the same method as compound 6a from 5-
methylisatin (6.02 g, 37 mmol) and octanoyl chloride (9.82 g,
55.5 mmol) as a brownish yellow solid (9.24 g, 87%). Mp 94e96 ꢀC;
4. Experimental
4.1. General
1H NMR (300 MHz, CDCl3):
d
0.88 (t, J¼7.0 Hz, 3H, CH2(CH2)5CH3),
1.24e1.46 (m, 8H, CH2CH2(CH2)4CH3), 1.68e1.78 (m, 2H,
CH2CH2(CH2)4CH3), 2.39 (s, 3H, ArCH3), 3.08 (t, J¼7.5 Hz, 2H,
CH2CH2(CH2)4CH3), 7.49e7.57 (m, 2H, ArH), 7.89 (d, J¼8.4 Hz, 1H,
Melting points were measured using a Reichert microscope
(Gallenkamp hot stage apparatus) and are uncorrected. Infrared

V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
8451
ArH); 13C NMR (75 MHz, CDCl3):
d
14.0 (CH2(CH2)5CH3), 22.3
(75 MHz, CDCl3):
d
14.1 (COCH2(CH2)5CH3), 20.7 (AreCH3), 22.6,
(ArCH3), 22.5, 24.0, 28.9, 31.6 (CH2(CH2)5CH3), 38.2
(COCH2(CH2)5CH3), 118.1, 125.2, 136.1 (ArCH), 119.2, 139.5, 146.8
(ArC), 158.0, 173.0, 180.4 (C]O); IR (KBr): nmax 2955, 2919, 2855,
1780, 1709, 1655, 1620, 1588, 1486, 1462, 1394, 1385, 1331, 1295,
1261, 1230, 1170, 1043, 993, 845 cmꢁ1; UV (DMF): lmax 260 (ε
25.5, 29.0, 29.2, 31.7 (COCH2(CH2)5CH3), 38.6 (COCH2), 118.3, 132.2,
140.0 (ArC), 120.8, 134.1, 137.7 (ArCH), 164.9, 172.5, 191.5 (C]O); IR
(KBr): nmax 3342, 3177, 2928, 2853, 1677, 1656, 1594, 1525, 1460,
1405, 1296, 1255, 1238, 1034, 936, 839, 795 cmꢁ1; UV (DMF): lmax
272 (ε 25,750 cmꢁ1 Mꢁ1), 348 (13,100); HRMS (ESI) m/z calculated
for C17H24N2O3Na (MþNa)þ 327.1787. Found 327.1676.
2900 cmꢁ1
M
ꢁ1), 272 (3700); HRMS (ESI) m/z calculated for
C17H22NO3 (MþH)þ 288.1521. Found 288.1589.
4.1.7. N-(2-(2-(Methylamino)-2-oxoacetyl)phenyl)octanamide 7d.
This compound was prepared by the same method as compound 7a
from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and methylamine
(0.06 g, 2 mmol) as an off-white solid (0.26 g, 67%). The solid,
recrystallized from methanol via slow evaporation of the solvent at
room temperature, yielded crystals suitable for X-ray crystal
structure determination. Mp 80e82 ꢀC; found: C, 67.24; H, 8.16; N,
9.27%, C17H24N2O3 requires C, 67.08; H, 7.95; N, 9.20%; 1H NMR
4.1.4. N-(2-(2-Amino-2-oxoacetyl)phenyl)octanamide 7a. A mixture
of N-octanoylisatin 6a (0.35 g, 1.28 mmol) and ammonia (0.08 g,
5 mmol) in dichloromethane (30 mL) was heated at reflux for
1e2 h. The cooled reaction mixture was concentrated in vacuo. The
crude product was purified by column chromatography using silica
gel and a mixture of dichloromethane and hexane as eluent. The
title compound was obtained as an off-white solid (0.23 g, 63%). The
solid, recrystallized from methanol via slow evaporation of the
solvent at room temperature, yielded crystals suitable for X-ray
crystal structure determination. Mp 152e154 ꢀC; found: C, 66.26;
H, 7.60; N, 9.59%, C16H22N2O3 requires C, 66.18; H, 7.64; N, 9.65%; 1H
(300 MHz, CDCl3):
d
0.86 (t, J¼7.0 Hz, 3H, COCH2CH2(CH2)4CH3),
1.22e1.36 (m, 8H, COCH2CH2(CH2)4CH3), 1.57e1.78 (m, 2H,
COCH2CH2(CH2)4CH3), 2.38 (t, J¼7.7 Hz, 2H, COCH2(CH2)5CH3), 2.96
(d, J¼5.1 Hz, 3H, NHCH3), 6.93 (s,1H, CONH), 7.06e7.12 (m,1H, ArH),
7.53e7.59 (m, 1H, ArH), 8.41 (dd, J¼8.1, 1.6 Hz, 1H, ArH), 8.64 (dd,
J¼8.5, 0.6 Hz, 1H, ArH), 10.93 (s, 1H, NHCO); 13C NMR (75 MHz,
NMR (300 MHz, CDCl3):
d
0.89 (t, J¼6.6 Hz, 3H,
COCH2CH2(CH2)4CH3), 1.18e1.36 (m, 8H, COCH2CH2(CH2)4CH3),
1.61e1.71 (m, 2H, COCH2CH2(CH2)4CH3), 2.42 (t, J¼7.7 Hz, 2H,
COCH2(CH2)5CH3), 6.19 (s, 1H, CONHH), 6.78 (s, 1H, CONHH),
7.03e7.08 (m, 1H, ArH), 7.50e7.56 (m, 1H, ArH), 8.22 (dd, J¼8.1,
1.4 Hz, 1H, ArH), 8.60 (dd, J¼8.6, 0.9 Hz, 1H, ArH), 10.86 (s, 1H,
CDCl3):
d 14.1 (COCH2(CH2)5CH3), 22.6, 25.5, 29.0, 29.2, 31.7
(COCH2(CH2)5CH3), 26.2 (NHCH3), 38.7 (COCH2), 118.7, 142.2 (ArC),
120.7, 122.4, 134.4, 136.6 (ArCH),163.6, 172.6, 193.0 (C]O); IR (KBr):
nmax 3284, 3252, 2926, 2853, 1698, 1665, 1608, 1533, 1485, 1406,
1337, 1301, 1248, 1212, 1080, 939, 867, 763 cmꢁ1; UV (DMF): lmax
231 (ε 4450 cmꢁ1 Mꢁ1), 261 (6800), 272 (8900), 338 (5000); HRMS
(ESI) m/z calculated for C17H24N2O3Na (MþNa)þ 327.1679. Found
327.1673.
NHCO); 13C NMR (75 MHz, CDCl3):
d 14.1 (COCH2(CH2)5CH3), 22.6,
25.5, 29.0, 29.2, 31.7 (COCH2(CH2)5CH3), 38.7 (COCH2), 118.2, 142.3
(ArC), 120.8, 122.5, 134.3, 136.8 (ArCH), 165.1, 172.7, 191.6 (C]O); IR
(KBr): nmax 3340, 3190, 2954, 2925, 2855, 1677, 1608, 1581, 1529,
1453, 1412, 1295, 1219, 1164, 1100, 979, 874, 808, 751 cmꢁ1; UV
(DMF): lmax 261 (ε 4500 cmꢁ1 Mꢁ1), 272 (7150), 338 (4100); HRMS
(ESI) m/z calculated for C16H23N2O3 (MþH)þ 291.1703. Found
291.1703.
4.1.8. N-(4-Bromo-2-(2-(methylamino)-2-oxoacetyl)phenyl)octana-
mide 7e. This compound was prepared by the same method as
compound 7a from N-octanoylisatin 6b (0.35 g, 1 mmol) and me-
thylamine (0.06 g, 2 mmol) as an off-white solid (0.23 g, 56%). Mp
136e138 ꢀC; found: C, 53.17; H, 5.94; N, 7.45%, C17H23BrN2O3 re-
4.1.5. N-(2-(2-Amino-2-oxoacetyl)-4-bromophenyl)octanamide 7b.
This compound was prepared by the same method as compound 7a
from N-octanoylisatin 6b (0.35 g, 1 mmol) and ammonia (0.08 g,
5 mmol) as an off-white solid (0.28 g, 72%). Mp 169e170 ꢀC; found:
C, 52.14; H, 5.56; N, 7.65%, C16H21BrN2O3 requires C, 52.04; H, 5.73;
quires C, 53.27; H, 6.05; N, 7.31%; 1H NMR (300 MHz, CDCl3):
d 0.86
(t, J¼7.0 Hz, 3H, COCH2CH2(CH2)4CH3), 1.23e1.34 (m, 8H,
COCH2CH2(CH2)4CH3), 1.66e1.76 (m, 2H, COCH2CH2(CH2)4CH3),
2.40 (t, J¼7.9 Hz, 2H, COCH2(CH2)5CH3), 2.98 (d, J¼5.1 Hz, 3H,
NHCH3), 6.87 (s, 1H, CONHCH3), 7.67 (dd, J¼9.2, 2.4 Hz, 1H, ArH),
8.58 (d, J¼0.6 Hz, 1H, ArH), 8.60 (d, J¼5.8 Hz, 1H, ArH), 10.83 (s, 1H,
N, 7.56%; 1H NMR (300 MHz, CDCl3):
d
0.86 (t, J¼7.0 Hz, 3H,
COCH2CH2(CH2)4CH3), 1.23e1.37 (m, 8H, COCH2CH2(CH2)4CH3),
1.67e1.77 (m, 2H, COCH2CH2(CH2)4CH3), 2.41 (t, J¼7.8 Hz, 2H,
COCH2(CH2)5CH3), 5.67 (s, 1H, CONHH), 6.70 (s, 1H, CONHH), 7.69
(dd, J¼9.1, 2.5 Hz, 1H, ArH), 8.54 (d, J¼2.3 Hz, 1H, ArH), 8.63 (d,
J¼9.1 Hz, 1H, ArH), 10.80 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
NHCO); 13C NMR (75 MHz, CDCl3):
d 14.1 (COCH2(CH2)5CH3), 22.6,
25.4, 29.0, 29.1, 31.7 (COCH2(CH2)5CH3), 26.3 (NHCH3), 38.7
(COCH2), 118.3, 132.2, 139.2 (ArC), 122.5, 134.3, 136.6 (ArCH), 161.9,
172.4, 190.6 (C]O); IR (KBr): nmax 3358, 3281, 2928, 2854, 1702,
1665, 1602,1525,1482, 1407,1382,1337,1282,1244, 1202,1074, 956,
870, 741 cmꢁ1; UV (DMF): lmax 261 (ε 3750 cmꢁ1 Mꢁ1), 272 (5800),
344 (2050); HRMS (ESI) m/z calculated for C17H23BrN2O3Na
(MþNa)þ 405.0784 (79Br). Found 405.0778 (79Br).
d
14.1 (COCH2(CH2)5CH3), 22.6, 25.4, 29.0, 29.1, 31.7
(COCH2(CH2)5CH3), 38.7 (COCH2), 118.3, 132.2, 134.1 (ArC), 122.5,
136.4, 139.4 (ArCH), 161.9, 169.1, 190.7 (C]O); IR (KBr): nmax 3341,
3249, 2928, 2852, 1696, 1678, 1658, 1603, 1577, 1518, 1460, 1394,
1290, 1242, 1205, 1095, 988, 837, 792 cmꢁ1; UV (DMF): lmax 236 (ε
3050 cmꢁ1
M
ꢁ1), 261 (4750), 272 (8350), 345 (3050); HRMS (ESI)
4.1.9. N-(4-Methyl-2-(2-(methylamino)-2-oxoacetyl)phenyl)octana-
mide 7f. This compound was prepared by the same method as
compound 7a from N-octanoylisatin 6c (0.37 g, 1.28 mmol) and
methylamine (0.06 g, 2 mmol) as an off-white solid (0.29 g, 71%).
Mp 110e112 ꢀC; found: C, 68.22; H, 8.51; N, 8.52%, C18H26N2O3 re-
m/z calculated for C16H21BrN2O3Na (MþNa)þ 391.0629 (79Br).
Found 391.0629 (79Br).
4.1.6. N-(2-(2-Amino-2-oxoacetyl)-4-methylphenyl)octanamide 7c.
This compound was prepared by the same method as compound 7a
from N-octanoylisatin 6c (0.37 g, 1.28 mmol) and ammonia (0.08 g,
5 mmol) as an off-white solid (0.23 g, 60%). Mp 133e135 ꢀC; found:
C, 67.27; H, 7.75; N, 9.11%, C17H24N2O3 requires C, 67.08; H, 7.95; N,
quires C, 67.90; H, 8.23; N, 8.80%; 1H NMR (300 MHz, CDCl3):
d 0.86
(t, J¼7.0 Hz, 3H, COCH2CH2(CH2)4CH3), 1.23e1.34 (m, 8H,
COCH2CH2(CH2)4CH3), 1.66e1.76 (m, 2H, COCH2CH2(CH2)4CH3),
2.40 (t, J¼7.8 Hz, 2H, COCH2(CH2)5CH3), 2.98 (d, J¼5.1 Hz, 3H,
NHCH3), 6.87 (s, 1H, CONHCH3), 7.67 (dd, J¼9.2, 2.4 Hz, 1H, ArH),
8.58 (d, J¼0.6 Hz, 1H, ArH), 8.60 (d, J¼5.8 Hz, 1H, ArH), 10.83 (s, 1H,
9.20%; 1H NMR (300 MHz, CDCl3):
d
0.86 (t, J¼6.8 Hz, 3H,
COCH2CH2(CH2)4CH3), 1.23e1.35 (m, 8H, COCH2CH2(CH2)4CH3),
1.61e1.75 (m, 2H, COCH2CH2(CH2)4CH3), 2.33 (s, 3H, ArCH3), 2.41 (t,
J¼7.8 Hz, 2H, COCH2(CH2)5CH3), 5.67 (s, 1H, CONHH), 6.62 (s, 1H,
CONHH), 7.43 (dd, J¼9.0, 1.6 Hz, 1H, ArH), 8.09 (d, J¼1.7 Hz, 1H,
ArH), 8.59 (d, J¼8.6 Hz, 1H, ArH), 10.79 (s, 1H, NHCO); 13C NMR
NHCO); 13C NMR (75 MHz, CDCl3):
d 14.2 (COCH2(CH2)5CH3), 20.8
(ArCH3), 22.6, 25.5, 29.0, 29.2, 31.7 (COCH2(CH2)5CH3), 26.22
(NHCH3), 38.6 (COCH2), 118.3, 132.2, 140.0 (ArC), 120.8, 134.3, 137.4
(ArCH), 164.5, 172.5, 191.4 (C]O); IR (KBr): nmax 3289, 3255, 2926,

8452
V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
2849, 1697, 1663, 1611, 1532, 1497, 1464, 1406, 1388, 1336, 1293,
6.75 (s, 1H, CONH), 7.42 (dd, J¼8.6, 2.2 Hz, 1H, ArH), 8.16 (d,
J¼1.7 Hz, 1H, ArH), 8.58 (d, J¼8.6 Hz, 1H, ArH), 10.86 (s, 1H, NHCO);
1249, 1200, 1081, 976, 821, 741 cmꢁ1; UV (DMF): lmax 236 (ε
2850 cmꢁ1
M
ꢁ1), 261 (4150), 274 (6500), 342 (3450); HRMS (ESI)
13C NMR (75 MHz, CDCl3):
d 13.7, 14.1 (COCH2(CH2)5CH3 and
m/z calculated for C18H27N2O3 (MþH)þ 319.2016. Found 319.2011.
NHCH2(CH2)4CH3), 20.7 (ArCH3), 22.6, 22.6, 25.5, 26.6, 29.0, 29.2,
29.3, 31.4, 31.7 (COCH2(CH2)5CH3 and NHCH2(CH2)4CH3), 38.7
(COCH2), 39.7 (NHCH2), 118.8, 132.0, 139.9 (ArC), 121.3, 134.8, 37.9
(ArCH), 162.8, 172.4, 192.2 (C]O); IR (KBr): nmax 3281, 2917, 2854,
1666, 1613, 1522, 1499, 1467, 1413, 1309, 1269, 1236, 1195, 1169,
821 cmꢁ1; UV (DMF): lmax 260 (ε 6750 cmꢁ1 Mꢁ1), 275 (9350), 347
(5700); HRMS (ESI) m/z calculated for C23H37N2O3 (MþH)þ
389.2726. Found 389.2787.
4.1.10. N-(2-(2-(Hexylamino)-2-oxoacetyl)phenyl)octanamide 7g. A
mixture of N-octanoylisatin 6a (0.35 g, 1.28 mmol) and hexylamine
(0.13 g, 1.28 mmol) in dichloromethane (30 mL) was heated at
reflux for 4e6 h. The cooled reaction mixture was concentrated in
vacuo. The crude product was purified by column chromatography
using silica gel and a mixture of dichloromethane and hexane as
eluent. The title compound was obtained as an off-white solid
(0.33 g, 71%). Mp 96e98 ꢀC; found: C, 70.26; H, 9.23; N, 7.45%,
C22H34N2O3 requires C, 70.55; H, 9.15; N, 7.48%, 1H NMR (300 MHz,
4.1.13. N-(2-(2-(Dodecylamino)-2-oxoacetyl)phenyl)octanamide
7j. This compound was prepared by the same method as com-
pound 7g from N-octanoylisatin 6a (0.27 g, 1 mmol) and dodecyl-
amine (0.18 g, 1 mmol) as an off-white solid (0.28 g, 60%). Mp
78e80 ꢀC; found: C, 73.10; H, 10.27; N, 6.15%, C28H46N2O3requires C,
CDCl3):
d
0.89
(m,
6H,
COCH2CH2(CH2)4CH3
and
NHCH2CH2(CH2)3CH3), 1.24e1.43 (m, 14H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)3CH3), 1.57e1.78 (m, 4H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)3CH3), 2.42 (t, J¼7.6 Hz, 2H, COCH2(CH2)5CH3),
3.37e3.44 (m, 2H, NHCH2CH2(CH2)3CH3), 6.83 (s, 1H, CONH),
7.09e7.14 (m, 1H, ArH), 7.56e7.62 (m, 1H, ArH), 8.41 (dd, J¼8.1,
1.6 Hz, 1H, ArH), 8.68 (dd, J¼8.5, 0.8 Hz, 1H, ArH), 10.96 (s, 1H,
73.32; H, 10.11; N, 6.11%; 1H NMR (300 MHz, CDCl3):
d 0.88 (m, 6H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)9CH3),1.21e1.43 (m, 26H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)9CH3), 1.56e1.78 (m, 4H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)9CH3), 2.41 (t, J¼7.8 Hz,
2H, COCH2(CH2)5CH3), 3.37e3.44 (m, 2H, NHCH2CH2(CH2)9CH3),
6.83 (t, J¼5.4 Hz, 1H, CONH), 7.08e7.14 (m, 1H, ArH), 7.6e7.6 (m, 1H,
ArH), 8.36 (dd, J¼8.0, 1.4 Hz, 1H, ArH), 8.68 (dd, J¼8.5, 0.9 Hz, 1H,
NHCO); 13C NMR (75 MHz, CDCl3):
d 13.9, 14.0 (COCH2(CH2)5CH3
and NHCH2(CH2)4CH3), 22.4, 22.5, 25.4, 26.5, 28.9, 29.1, 29.2, 31.3,
31.6 (COCH2(CH2)5CH3 and NHCH2(CH2)4CH3), 38.6 (COCH2), 39.6
(NHCH2), 118.5, 142.2 (ArC), 120.6, 122.3, 134.4, 136.5 (ArCH), 162.8,
172.4, 192.1 (C]O); IR (KBr): nmax 3289, 3176, 3113, 927, 2855, 1689,
1666, 1605, 1527, 1483, 1468, 1411, 1377, 1316, 1255, 1214, 1078, 946,
ArH), 10.99 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
d 13.9, 14.0
(COCH2(CH2)5CH3 and NHCH2(CH2)10CH3), 22.5, 22.6, 25.4, 26.8,
28.9, 29.6, 29.1, 29.2, 29.4, 29.5, 29.5, 31.6, 31.8 (COCH2(CH2)5CH3
and NHCH2(CH2)10CH3), 38.6 (COCH2), 39.6 (NHCH2), 118.6, 142.2
(ArC), 120.6, 122.3, 134.4, 136.5 (ArCH), 162.8, 172.4, 192.1 (C]O); IR
(KBr): nmax 3281, 2919, 2852, 1665, 1605, 1526, 1485, 1467, 1412,
1377, 1320, 1267, 1248, 1158, 1112, 1077, 966, 948, 757 cmꢁ1; UV
(DMF): lmax 260 (ε 5550 cmꢁ1 Mꢁ1), 274 (7750), 340 (4850); HRMS
(ESI) m/z calculated for C28H47N2O3 (MþH)þ 459.3508. Found
459.3571.
823, 757 cmꢁ1; UV (DMF): lmax 261 (ε 9100 cmꢁ1
M
ꢁ1), 270
(13,250), 348 (5100); MS (TOF-ESI) m/z calculated for C22H35N2O3
(MþH)þ 375.25. Found 375.26.
4.1.11. N-(4-Bromo-2-(2-(hexylamino)-2-oxoacetyl)phenyl)octana-
mide 7h. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6b (0.35 g, 1 mmol) and hex-
ylamine (0.10 g, 1 mmol) as an off-white solid (0.29 g, 64%). Mp
150e152 ꢀC; found: C, 58.47; H, 7.37; N, 6.30%, C22H33BrN2O3 re-
4.1.14. N-(4-Bromo-2-(2-(dodecylamino)-2-oxoacetyl)phenyl)octa-
namide 7k. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6b (0.35 g, 1 mmol) and
dodecylamine (0.18 g, 1 mmol) as an off-white solid (0.36 g, 67%).
The solid, recrystallized from methanol via slow evaporation of the
solvent at room temperature, yielded crystals suitable for X-ray
crystal structure determination. Mp 142e144 ꢀC; found: C, 62.72; H,
8.47; N, 5.27%, C28H45BrN2O3 requires C, 62.56; H, 8.44; N, 5.21%; 1H
quires C, 58.28; H, 7.34; N, 6.18%; 1H NMR (300 MHz, CDCl3):
d 0.89
(m, 6H, COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)4CH3), 1.24e1.43
(m, 14H, COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)3CH3), 1.57e1.78
(m, 4H, COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)3CH3), 2.41 (t,
J¼7.7
Hz, 2H, COCH2(CH2)5CH3),
NHCH2CH2(CH2)3CH3), 6.86 (s, 1H, CONH), 7.68 (dd, J¼9.1, 2.4 Hz,
3.37e3.44 (m,
2H,
1H, ArH), 8.59e8.63 (m, 2H, ArH), 10.86 (s, 1H, NHCO); 13C NMR
(75 MHz, CDCl3):
d
13.9, 14.0 (COCH2(CH2)5CH3 and
NMR (300 MHz, CDCl3): d 0.88 (m, 6H, COCH2CH2(CH2)4CH3 and
NHCH2(CH2)4CH3), 22.4, 22.5, 25.3, 26.5, 28.9, 29.0, 29.1, 31.3, 31.6
(COCH2(CH2)5CH3 and NHCH2(CH2)4CH3), 38.6 (COCH2), 39.7
(NHCH2), 114.7, 122.4, 141.1 (ArC), 120.2, 136.5, 139.0 (ArCH), 161.8,
172.4, 190.6 (C]O); IR (KBr): nmax 3280, 3172, 2927, 2872, 2853,
1666, 1596, 1544, 1515, 1482, 1412, 1380, 1294, 1260, 1244, 1207,
NHCH2CH2(CH2)9CH3),1.21e1.43 (m, 26H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)9CH3), 1.56e1.78 (m, 4H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)9CH3), 2.41 (t, J¼7.7 Hz, 2H, COCH2(CH2)5CH3),
3.37e3.44 (m, 2H, NHCH2CH2(CH2)9CH3), 6.87 (s, 1H, CONH), 7.68
(dd, J¼9.0, 2.5 Hz, 1H, ArH), 8.59e8.63 (m, 2H, ArH), 10.87 (s, 1H,
1131, 895, 828 cmꢁ1; UV (DMF): lmax 230 (ε 300 cmꢁ1
M
ꢁ1), 337
NHCO); 13C NMR (75 MHz, CDCl3):
d 13.9,14.0 (COCH2(CH2)5CH3 and
(450); HRMS (ESI) m/z calculated for C22H34BrN2O3 (MþH)þ
NHCH2(CH2)10CH3), 22.5, 22.6, 25.3, 26.8, 28.9, 29.0, 29.1, 29.2, 29.3,
29.4, 29.5, 29.5, 31.6, 31.8 (COCH2(CH2)5CH3 and NHCH2(CH2)10CH3),
38.6 (COCH2), 39.7 (NHCH2), 114.7, 122.3, 141.1 (ArC), 120.1, 136.5,
139.0 (ArCH), 161.9, 172.4, 190.6 (C]O); IR (KBr): nmax 3276, 2921,
2851, 1667, 1596, 1514, 1481, 1412, 1379, 1294, 1245, 1207, 1130, 952,
826, 755 cmꢁ1; UV (DMF): lmax 259 (ε 3900 cmꢁ1 Mꢁ1), 269 (16,100),
344 (5750); HRMS (ESI) m/z calculated for C28H46BrN2O3 (MþH)þ
537.2614 (79Br). Found 537.2673 (79Br).
453.1675 (79Br). Found 453.1736 (79Br).
4.1.12. N-(2-(2-(Hexylamino)-2-oxoacetyl)-4-methylphenyl)octana-
mide 7i. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6c (0.37 g, 1.28 mmol) and
hexylamine (0.13 g, 1.28 mmol) as a white solid (0.36 g, 73%). The
solid, recrystallized from methanol via slow evaporation of the
solvent at room temperature, yielded crystals suitable for X-ray
crystal structure determination. Mp 125e127 ꢀC; found: C, 71.17; H,
9.34; N, 7.36%, C23H36N2O3 requires C, 71.10; H, 9.34; N, 7.21%; 1H
4.1.15. N-(2-(2-(Dodecylamino)-2-oxoacetyl)-4-methylphenyl)octa-
namide 7l. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6c (0.29 g, 1 mmol) and dode-
cylamine (0.18 g,1 mmol)asan off-white solid(0.31 g, 66%). The solid,
recrystallized from methanol via slow evaporation of the solvent at
room temperature, yielded crystals suitable for X-ray crystal struc-
ture determination. Mp 92e94 ꢀC; found: C, 73.74; H,10.43; N, 6.04%,
NMR (300 MHz, CDCl3):
d 0.85e0.92 (m, 6H, COCH2CH2(CH2)4CH3
and NHCH2CH2(CH2)3CH3), 1.24e1.36 (m, 14H, COCH2CH2(CH2)4CH3
and NHCH2CH2(CH2)3CH3), 1.57e1.78 (m, 4H, COCH2CH2(CH2)4CH3
and NHCH2CH2(CH2)3CH3), 2.34 (s, 3H, AreCH3), 2.40 (t, J¼7.8 Hz,
2H, COCH2(CH2)5CH3), 3.37e3.44 (m, 2H, NHCH2CH2(CH2)3CH3),

V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
8453
C29H48N2O3 requires C, 73.68; H,10.23; N, 5.93%; 1H NMR (300 MHz,
CDCl3):
0.88 (t, J¼6.92 Hz, 6H, COCH2CH2(CH2)4CH3 and
octadecylamine (0.27 g, 1 mmol) as an off-white solid (0.31 g, 56%).
Mp 78e80 ꢀC; found: C, 75.55; H, 11.04; N, 5.15%, C35H60N2O3 re-
quires C, 75.49; H, 10.86; N, 5.03%; 1H NMR (300 MHz, CDCl3):
d
NHCH2CH2(CH2)9CH3), 1.23e1.38 (m, 26H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)9CH3), 1.61e1.78 (m, 4H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)9CH3), 2.34 (s, 3H, ArCH3), 2.41 (t, J¼7.8 Hz, 2H,
COCH2(CH2)5CH3), 3.37e3.44 (m, 2H, NHCH2CH2(CH2)9CH3), 6.87 (t,
J¼5.4 Hz, 1H, CONH), 7.42 (dd, J¼8.6, 2.0 Hz, 1H, ArH), 8.16 (d,
J¼1.8 Hz,1H, ArH), 8.58 (d, J¼8.6 Hz,1H, ArH),10.86 (s,1H, NHCO); 13C
d
0.87 (t, J¼6.67 Hz, 6H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)15CH3), 1.23e1.36 (m, 38H, COCH2CH2(CH2)4CH3
and NHCH2CH2(CH2)15CH3), 1.57e1.77 (m, 4H, COCH2CH2(CH2)4CH3
and NHCH2CH2(CH2)15CH3), 2.33 (s, 3H, ArCH3), 2.39 (t, J¼7.8 Hz,
2H, COCH2(CH2)5CH3), 3.37e3.44 (m, 2H, NHCH2CH2(CH2)15CH3),
6.84 (t, J¼5.3 Hz, 1H, CONH), 7.39 (dd, J¼8.5, 2.1 Hz, 1H, AreH), 8.11
(d, J¼1.7 Hz, 1H, ArH), 8.55 (d, J¼8.7 Hz, 1H, ArH), 10.86 (s, 1H,
NMR (75 MHz, CDCl3):
d 13.8, 14.1 (COCH2(CH2)5CH3 and
NHCH2(CH2)10CH3), 20.7 (ArCH3), 22.6, 22.7, 25.5, 26.9, 29.0, 29.2,
29.3, 29.3, 29.4, 29.6, 29.6, 29.6, 31.7, 31.9 (COCH2(CH2)5CH3 and
NHCH2(CH2)10CH3), 38.7 (COCH2), 39.7 (NHCH2), 118.7, 132.0, 139.9
(ArC), 121.3, 134.8, 137.8 (ArCH), 163.1, 172.4, 192.3 (C]O); IR (KBr):
nmax 3276, 3086, 2919, 2852, 1665, 1612, 1521, 1500, 1467, 1413, 1378,
1301, 1271, 1248, 1169, 950, 822, 712 cmꢁ1; UV (DMF): lmax 264 (ε
NHCO); 13C NMR (75 MHz, CDCl3):
d 13.8, 14.1 (COCH2(CH2)5CH3
and NHCH2(CH2)16CH3), 22.6, 22.7, 25.5, 26.9, 29.0, 29.1, 29.2, 29.3,
29.4, 29.6, 29.7, 31.7, 31.9 (COCH2(CH2)5CH3 and NHCH2(CH2)16CH3),
20.7 (ArCH3), 38.7 (COCH2), 39.7 (NHCH2), 118.8, 132.0, 139.9 (ArC),
121.3, 134.8, 137.4 (ArCH), 163.0, 172.3, 192.2 (C]O); IR (KBr): nmax
3323, 2916, 2849, 1701, 1663, 1642, 1589, 1523, 1469, 1418, 1376,
1327, 1295, 1231, 1162, 846, 781 cmꢁ1; UV (DMF): lmax 275 (ε
9250 cmꢁ1
M
ꢁ1), 271 (12,900), 348 (6850); HRMS (ESI) m/z calcu-
lated for C29H49N2O3 (MþH)þ 473.3665. Found 473.3725.
9800 cmꢁ1
M
ꢁ1), 346 (5700); HRMS (ESI) m/z calculated for
4.1.16. N-(2-(2-(Octadecylamino)-2-oxoacetyl)phenyl)octanamide
7m. This compound was prepared by the same method as com-
pound 7g from N-octanoylisatin 6a (0.27 g, 1 mmol) and octadecyl-
amine (0.27 g, 1 mmol) as an off-white solid (0.32 g, 59%). Mp
68e70 ꢀC; found: C, 75.30; H,11.00; N, 5.33%, C34H58N2O3 requires C,
C35H61N2O3 (MþH)þ 557.4604. Found 557.4660.
4.1.19. Methyl 2-(2-(2-octanamidophenyl)-2-oxoacetamido)acetate
9a. A solution of glycine methyl ester hydrochloride (0.40 g,
3.2 mmol) containing saturated NaHCO3 was added to a stirred
solution of the N-octanoylisatin 6a (0.35 g, 1.28 mmol) in
dichloromethane (25 mL) at 5 ꢀC. The reaction mixture was
warmed to room temperature and stirred for 24e28 h. The organic
layer was diluted with CH2Cl2 (25 mL) and washed with aqueous
HCl (0.5 M, 15 mL) and water (20 mL). The organic extract was dried
over anhydrous Na2SO4, filtered and concentrated under vacuum.
The crude product was purified by column chromatography using
silica gel and a mixture of dichloromethane and hexane as eluent.
The title compounds was obtained as an off-white solid (0.21 g,
46%). The solid, recrystallized from methanol via slow evaporation
of the solvent at room temperature, yielded crystals suitable for X-
ray crystal structure determination. Mp 82e84 ꢀC; found: C, 63.09;
H, 7.24; N, 7.79%, C19H26N2O5 requires C, 62.97; H, 7.23; N, 7.73%; 1H
75.23; H, 10.77; N, 5.16%; 1H NMR (300 MHz, CDCl3):
d 0.88 (m, 6H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)15CH3),1.21e1.43 (m, 38H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)15CH3), 1.56e1.79 (m, 4H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)15CH3), 2.42 (t, J¼7.8 Hz,
2H, COCH2(CH2)4CH3), 3.37e3.44 (m, 2H, NHCH2CH2(CH2)15CH3),
6.81 (t, J¼5.7 Hz, 1H, CONH), 7.08e7.14 (m, 1H, ArH), 7.56e7.62 (m,
1H, ArH), 8.36 (dd, J¼8.1,1.42 Hz,1H, ArH), 8.69 (dd, J¼8.6, 0.9 Hz,1H,
ArH), 10.99 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
d 13.9, 14.0
(COCH2(CH2)5CH3 andNHCH2(CH2)16CH3), 22.5, 22.6, 25.4, 26.8, 28.8,
29.0, 29.1, 29.2, 29.3, 29.4, 29.5, 29.6, 31.6, 31.8 (COCH2(CH2)5CH3 and
NHCH2(CH2)16CH3), 38.6 (COCH2), 39.6 (NHCH2), 118.6, 142.2 (ArC),
120.6, 122.3, 134.4, 136.5 (ArCH), 162.7, 172.4, 192.0 (C]O); IR (KBr):
nmax 3321, 2918, 2850, 1710, 1641, 1604, 1585, 1529, 1468, 1376, 1312,
1295, 1213, 1160, 921, 862, 760, 721 cmꢁ1; UV (DMF): lmax 258 (ε
NMR (300 MHz, CDCl3):
d
0.86 (t, J¼7.0 Hz, 3H,
8650 cmꢁ1
M
ꢁ1), 272 (12,200), 337 (7250); HRMS (ESI) m/z calcu-
COCH2CH2(CH2)4CH3), 1.23e1.35 (m, 8H, COCH2CH2(CH2)4CH3),
1.66e1.79 (m, 2H, COCH2CH2(CH2)4CH3), 2.42 (t, J¼7.7 Hz, 2H,
COCH2(CH2)5CH3), 3.80 (s, 3H, COCH3), 4.18 (d, J¼5.4 Hz, 2H,
NHCH2COO), 7.08e7.14 (m, 1H, ArH), 7.23 (s, 1H, CONH), 7.57e7.63
(m, 1H, ArH), 8.36 (dd, J¼8.1, 1.5 Hz, 1H, ArH), 8.71 (dd, J¼8.3, 1.5 Hz,
lated for C34H59N2O3 (MþH)þ 543.4447. Found 543.4517.
4.1.17. N-(4-Bromo-2-(2-(octadecylamino)-2-oxoacetyl)phenyl)octa-
namide 7n. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6b (0.35 g, 1 mmol) and
octadecylamine (0.27 g, 1 mmol) as an off-white solid (0.34 g, 55%).
Mp 298e300 ꢀC; found: C, 65.86; H, 9.24; N, 4.50%, C34H57BrN2O3
requires C, 65.68; H, 9.24; N, 4.51%; 1H NMR (300 MHz, CDCl3):
1H, ArH), 10.96 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
d 14.0
(COCH2(CH2)5CH3), 22.6, 25.5, 29.0, 29.2, 31.7 (COCH2(CH2)5CH3),
38.7 (CH2CONH), 41.2 (NHCH2COO), 52.7 (COOCH3), 118.3, 142.5
(ArC),120.7,122.4,134.5,136.9 (ArCH),162.9,169.4,172.6,190.9 (C]
O); IR (KBr): nmax 3284, 2919, 2856, 1763, 1697, 1664, 1606, 1527,
1481, 1437, 1407, 1369, 1313, 1267, 1201, 1180, 1030, 940, 806,
771 cmꢁ1; UV (MeOH): lmax 235 (ε 17,400 cmꢁ1 Mꢁ1), 272 (7700),
344 (4500); HRMS (ESI) m/z calculated for C19H27N2O5 (MþH)þ
363.1842. Found 363.1910.
d
0.88 (m, 6H, COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)15CH3),
1.21e1.43 (m, 38H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)15CH3), 1.56e1.78 (m, 4H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)15CH3), 2.43 (t, J¼7.8 Hz, 2H, COCH2(CH2)4CH3),
3.37e3.44 (m, 2H, NHCH2CH2(CH2)15CH3), 6.88 (t, J¼5.3 Hz, 1H,
CONH), 7.68 (dd, J¼9.1, 2.4 Hz, 1H, ArH), 8.58e8.63 (m, 2H, ArH),
10.87 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
d
13.9, 14.0
4.1.20. Methyl 2-(2-(2-octanamidophenyl)-2-oxoacetamido)propano
(COCH2(CH2)5CH3 and NHCH2(CH2)16CH3), 22.5, 22.6, 25.3, 26.8,
28.9, 29.0, 29.1, 29.2, 29.3, 29.4, 29.5, 29.6, 31.6, 31.8
(COCH2(CH2)5CH3 and NHCH2(CH2)16CH3), 38.6 (COCH2), 39.7
(NHCH2), 114.7, 122.3, 141.1 (ArC), 120.1, 136.5, 139.0 (ArCH), 161.9,
172.4, 190.6 (C]O); IR (KBr): nmax 3406, 3282, 2920, 2850, 2358,
2342, 1667, 1646, 1597, 1518, 1469, 1412, 1393, 1288, 1248, 1159,
1099, 966, 826, 720 cmꢁ1; UV (DMF): lmax 261 (ε 32,050 cmꢁ1 Mꢁ1),
271 (48,600), 347 (20,700); HRMS (ESI) m/z calculated for
C34H58BrN2O3 (MþH)þ 621.3553 (79Br). Found 621.3622 (79Br).
ate 9b. This compound was prepared by the same method as
compound 9a from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and L-
alanine methyl ester hydrochloride (0.45 g, 3.2 mmol) as an off-
white solid (0.19 g, 52%). Mp 48e50 ꢀC; found: C, 63.99; H, 7.64;
N, 7.53%, C20H28N2O5 requires C, 63.81; H, 7.50; N, 7.44%; 1H NMR
(300 MHz, CDCl3):
d
0.86 (t, J¼6.66 Hz, 3H, COCH2CH2(CH2)4CH3),
1.23e1.40 (m, 8H, COCH2CH2(CH2)4CH3), 1.52 (d, J¼5.4 Hz, 3H,
NHCHCH3COO), 1.68e1.78 (m, 2H, COCH2CH2(CH2)4CH3), 2.42 (t,
J¼7.7 Hz, 2H, COCH2(CH2)5CH3), 3.79 (s, 3H, COCH3), 4.62e4.71 (m,
1H, NHCHCH3COO), 7.08e7.14 (m, 1H, ArH), 7.23 (d, J¼7.2 Hz, 1H,
CONH), 7.57e7.63 (m, 1H, ArH), 8.36 (dd, J¼8.3, 1.6 Hz, 1H, ArH),
8.71 (dd, J¼8.5, 0.7 Hz, 1H, ArH), 10.97 (s, 1H, NHCO); 13C NMR
4.1.18. N-(4-Methyl-2-(2-(octadecylamino)-2-oxoacetyl)phenyl)oc-
tanamide 7o. This compound was prepared by the same method as
compound 7g from N-octanoylisatin 6c (0.29 g, 1 mmol) and
(75 MHz, CDCl3):
d 14.1 (COCH2(CH2)5CH3), 18.1 (NHCHCH3COO),

8454
V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
22.6, 25.5, 29.0, 29.2, 31.7 (COCH2(CH2)5CH3), 38.8 (CH2CONH), 48.3
(NHCHCH3COO), 52.8 (COOCH3), 118.3, 142.5 (ArC), 120.7, 122.4,
134.5, 136.8 (ArCH), 162.2, 172.5, 172.6, 191.1 (C]O); IR (KBr): nmax
3283, 2923, 2852, 1738, 1709, 1650, 1604, 1582, 1526, 1448, 1347,
1277, 1214, 1067, 977, 873, 760 cmꢁ1; UV (MeOH): lmax 234 (ε
(m, 4H, COCH2CH2(CH2)4CH3 and NHCH2CH2CH2CH3), 2.42 (t,
J¼7.9 Hz, 2H, COCH2(CH2)5CH3), 4.14e4.22 (m, 2H,
NHCH2CH2CH2CH3), 4.60e4.70 (m, 1H, NHCHCH3COO), 7.06e7.11
(m, 1H, ArH), 7.43 (d, J¼7.4 Hz, 1H, CONH), 7.54e7.59 (m, 1H, ArH),
8.30 (dd, J¼8.1, 1.5 Hz, 1H, ArH), 8.68 (dd, J¼8.6, 0.9 Hz, 1H, ArH),
10.98 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3): 13.7, 14.1
(COCH2(CH2)5CH3 and NHCH2(CH2)2CH3), 18.1 (NHCHCH3COO),
19.3, 22.6, 25.5, 29.0, 29.2, 30.6, 31.7 (COCH2(CH2)5CH3 and
NHCH2(CH2)2CH3), 38.7 (CH2CONH), 48.4 (NHCHCH3COO), 65.7
(COOCH2), 118.3, 142.4 (ArC),120.6,122.4, 134.4, 136.7 (ArCH),162.6,
172.1, 172.6, 191.5 (C]O); IR (KBr): nmax 3288, 2922, 2868, 1753,
1706, 1661, 1640, 1587, 1533,1451, 1376, 1312, 1276, 1205, 1162, 1067,
14,700 cmꢁ1
M
ꢁ1), 271 (6900), 343 (4100); HRMS (ESI) m/z calcu-
lated for C20H29N2O5 (MþH)þ 377.1998. Found 377.2059.
4.1.21. Butyl
2-(2-(2-octanamidophenyl)-2-oxoacetamido)acetate
9c. This compound was prepared by the same method as com-
pound 9a from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and glycine
butyl ester hydrochloride 112 (0.59 g, 3.2 mmol) as an off-white
solid (0.23 g, 44%). Mp 88e90 ꢀC; found: C, 65.59; H, 8.23; N,
6.88%, C22H32N2O5 requires C, 65.32; H, 7.97; N, 6.93%; 1H NMR
878, 764 cmꢁ1; UV (MeOH): lmax 234 (ε 25,900 cmꢁ1
M
ꢁ1), 272
(10,500), 344 (5900); MS (TOF-ESI) m/z calculated for C23H35N2O5
(300 MHz, CDCl3):
d 0.89e1.01 (m, 6H, COCH2CH2(CH2)4CH3 and
(MþH)þ 419.25. Found 419.21.
NHCH2(CH2)2CH3), 1.28e1.50 (m, 10H, COCH2CH2(CH2)4CH3 and
NHCH2CH2CH2CH3), 1.66e1.81 (m, 4H, COCH2CH2(CH2)4CH3 and
NHCH2CH2CH2CH3), 2.42 (t, J¼7.8 Hz, 2H, COCH2(CH2)5CH3),
4.21e4.28 (m, 4H, NHCH2COO and NHCH2CH2CH2CH3), 7.14e7.19
(m, 1H, ArH), 7.31 (s, 1H, CONH), 7.63e7.69 (m, 1H, ArH), 8.36 (dd,
J¼8.1, 1.6 Hz, 1H, ArH), 8.71 (dd, J¼8.6, 1.0 Hz, 1H, ArH), 11.02 (s, 1H,
4.1.24. Hexyl 2-(2-(2-octanamidophenyl)-2-oxoacetamido)propano
ate 9f. This compound was prepared by the same method as
compound 9a from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and L-
alanine hexyl ester hydrochloride (0.67 g, 3.2 mmol) as an off-white
solid (0.31 g, 55%). Mp 32e34 ꢀC; found: C, 67.30; H, 8.79; N, 6.42%,
C25H38N2O5 requires C, 67.24; H, 8.58; N, 6.27%; 1H NMR (300 MHz,
NHCO); 13C NMR (75 MHz, CDCl3):
d 13.7, 14.1 (COCH2(CH2)5CH3
and NHCH2(CH2)2CH3), 19.1, 22.6, 25.5, 29.0, 29.2, 30.6, 31.7
(COCH2(CH2)5CH3 and NHCH2(CH2)2CH3), 39.4 (CH2CONH), 41.9
(NHCH2COO), 66.2 (COOCH2), 118.6, 142.8 (ArC), 120.4, 122.8, 134.7,
137.2 (ArCH), 163.2, 169.2, 172.7, 191.4 (C]O); IR (KBr): nmax 3282,
2921, 2858, 1760, 1695, 1663, 1605, 1526, 1481, 1466, 1409, 1364,
1312, 1243, 1029, 941, 772 cmꢁ1; UV (MeOH): lmax 234 (ε
CDCl3):
d
0.85e0.93 (m, 6H, COCH2CH2(CH2)4CH3 and
NHCH2(CH2)4CH3), 1.24e1.41 (m, 14H, COCH2CH2(CH2)4CH3 and
NHCH2CH2(CH2)3CH3), 1.54 (d, J¼7.2 Hz, 3H, NHCHCH3COO),
1.63e1.79 (m, 4H, COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)3CH3),
2.42 (t, J¼7.9 Hz, 2H, COCH2(CH2)5CH3), 4.13e4.25 (m, 2H,
NHCH2CH2(CH2)3CH3), 4.61e4.72 (m, 1H, NHCHCH3COO), 7.09e7.16
(m, 1H, ArH), 7.32 (d, J¼7.6 Hz, 1H, CONH), 7.58e7.64 (m, 1H, ArH),
8.30 (dd, J¼8.1, 1.6 Hz, 1H, ArH), 8.73 (dd, J¼8.6, 0.9 Hz, 1H, ArH),
20,050 cmꢁ1
M
ꢁ1), 273 (8850), 343 (5200); HRMS (ESI) m/z cal-
culated for C22H33N2O5 (MþH)þ 405.2311. Found 405.2382.
10.99 (s, 1H, NHCO); 13C NMR (75 MHz, CDCl3):
d 13.7, 14.1
4.1.22. Hexyl 2-(2-(2-octanamidophenyl)-2-oxoacetamido)acetate
9e. This compound was prepared by the same method as com-
pound 9a from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and glycine
hexyl ester hydrochloride (0.63 g, 3.2 mmol) as a yellowish solid
(0.23 g, 42%). The solid, recrystallized from methanol via slow
evaporation of the solvent at room temperature, yielded crystals
suitable for X-ray crystal structure determination. Mp 56e58 ꢀC;
found: C, 66.46; H, 8.35; N, 6.46%, C24H36N2O5 requires C, 66.64; H,
(COCH2(CH2)5CH3 and NHCH2(CH2)4CH3), 18.2 (NHCHCH3COO),
22.5, 22.6, 25.5, 25.5, 28.5, 29.0, 29.2, 31.4, 31.7 (COCH2(CH2)5CH3
and NHCH2(CH2)4CH3), 48.5 (NHCHCH3COO), 38.8 (CH2CONH); IR
(KBr): nmax 3301, 2927, 2856, 2359, 1752, 1707, 1661, 1642, 1586,
1531, 1451, 1377, 1274, 1205, 1066, 876, 763 cmꢁ1; 66.1 (COOCH2),
118.3, 142.5 (ArC), 120.7, 122.4, 134.5, 136.8 (ArCH), 162.3, 172.1,
172.6, 191.3 (C]O); UV (MeOH): lmax 234 (ε 24,950 cmꢁ1 Mꢁ1), 273
(10,900), 342 (6300); MS (TOF-ESI) m/z calculated for C25H39N2O5
(MþH)þ 447.28. Found 447.23.
8.39; N, 6.48%; 1H NMR (300 MHz, CDCl3):
d 0.85e0.92 (m, 6H,
COCH2CH2(CH2)4CH3 and NHCH2(CH2)4CH3), 1.26e1.40 (m, 14H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)3CH3), 1.61e1.78 (m, 4H,
COCH2CH2(CH2)4CH3 and NHCH2CH2(CH2)3CH3), 2.41 (t, J¼7.8 Hz,
2H, COCH2(CH2)5CH3), 4.21e4.28 (m, 4H, NHCH2COO and
NHCH2CH2(CH2)3CH3), 7.07e7.13 (m, 1H, ArH), 7.31 (t, J¼5.1 Hz, 1H,
CONH), 7.55e7.61 (m,1H, ArH), 8.34 (dd, J¼8.1,1.6 Hz,1H, ArH), 8.69
(dd, J¼8.6, 0.9 Hz, 1H, ArH), 10.97 (s, 1H, NHCO); 13C NMR (75 MHz,
4.2. Structure determination
Suitable single crystals of 7a, 7k, 7l and 9a selected under the
polarizing microscope (Leica M165Z), were picked up on a Micro-
Mount (MiTeGen, USA) consisting of a thin polymer tip with
a wicking aperture. The X-ray diffraction measurements were car-
ried out on a Bruker KAPPA APEX II CCD diffractometer at 150 K by
using graphite-monochromated Mo-K
The single crystals, mounted on the goniometer using cryo loops for
intensity measurements, were coated with paraffin oil and then
quickly transferred to the cold stream using an Oxford Cryo stream
attachment. Symmetry related absorption corrections using the
program SADABS38 were applied and the data were corrected for
Lorentz and polarization effects using Bruker APEX2 software.39 All
structures were solved by direct methods and the full-matrix least-
squares refinements were carried out using SHELXL.40 The non-
hydrogen atoms were refined anisotropically. The molecular
graphics were generated using mercury.41
CDCl3):
d
14.0, 14.1 (COCH2(CH2)5CH3 and NHCH2(CH2)4CH3), 22.5,
ꢀ
22.6, 25.5, 28.5, 29.0, 29.2, 31.4, 31.7 (COCH2(CH2)5CH3 and
NHCH2(CH2)4CH3), 38.7 (CH2CONH), 41.0 (NHCH2COO), 66.1
(COOCH2), 118.3, 142.4 (ArC), 120.6, 122.4, 134.5, 136.8 (ArCH), 163.1,
169.0, 172.6, 191.2 (C]O); IR (KBr): nmax 3337, 2923, 2855, 1757,
1706, 1663, 1643, 1606, 1586, 1532, 1468, 1451, 1417, 1359, 1259,
a
radiation (
l
¼0.710723 A).
1194, 1130, 958, 815, 753 cmꢁ1
; UV (MeOH): lmax 235(ε
24,400 cmꢁ1
M
ꢁ1), 273 (11,400), 344 (6850); MS (TOF-ESI) m/z
calculated for C24H37N2O5 (MþH)þ 433.26. Found 433.29.
4.1.23. Butyl 2-(2-(2-octanamidophenyl)-2-oxoacetamido)propano
ate 9e. This compound was prepared by the same method as
compound 9a from N-octanoylisatin 6a (0.35 g, 1.28 mmol) and
L
-
The X-ray diffraction measurements for 7d, 7i and 9d were
carried out at MX1 and MX2 beamlines at the Australian Syn-
chrotron Facility, Melbourne. The procedure for diffraction in-
tensity measurements on both beamlines was similar. The crystal
was mounted on the goniometer using a cryo loop for diffraction
measurements, was coated with paraffin oil and then quickly
transferred to the cold stream using Cryo stream attachment. Data
alanine butyl ester hydrochloride (0.58 g, 3.2 mmol) as an off-white
solid (0.30 g, 56%). Mp 42e44 ꢀC; found: C, 66.05; H, 8.38; N, 6.63%,
C23H34N2O5 requires C, 66.00; H, 8.19; N, 6.69%; 1H NMR (300 MHz,
CDCl3):
d
0.84e0.96 (m, 6H, COCH2CH2(CH2)4CH3 and
NHCH2(CH2)2CH3), 1.24e1.45 (m, 10H, COCH2CH2(CH2)4CH3 and
NHCH2CH2CH2CH3),1.52 (d, J¼7.2 Hz, 3H, NHCHCH3COO),1.60e1.78

V. Suryanti et al. / Tetrahedron 69 (2013) 8446e8455
8455
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were collected using Si<111> monochromated synchrotron X-ray
ꢀ
radiation (l¼0.71023 A) at 100(2) K and were corrected for Lorentz
and polarization effects using the XDS software.42 The structure
was solved by direct methods and the full-matrix least-squares
refinements were carried out using SHELXL.40
10. Suryanti, V.; Bhadbhade, M.; Bishop, R.; Black, D. StC.; Kumar, N. CrystEngComm
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Acknowledgements
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We thank the Directorate General of Higher Education, Ministry
of National Education, Indonesia through the University of Sebelas
Maret, Indonesia for a PhD scholarship to Venty Suryanti. We also
thank Dr. Tom Caradoc-Davies, a Principal Scientist (Australian
Synchrotron), for his help in data acquisition. Financial support
from the University of New South Wales and the Australian Re-
search Council (Project Number DP1095159) is gratefully
acknowledged.
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Supplementary data
Fig. S1 shows the crystal structures of 7a, 7d, 7i, 7k and 7l. Fig. S2
shows the crystal packings of 7a, 7d, 7i and 7l. The geometric pa-
rameters of the intramolecular interactions are summarized given
in Table S1. The intermolecular interaction distances and angles of
7a, 7d, 7i, 7k, 7l, 9a and 9d are listed in Table S2. X-ray crystallo-
graphic information files (CIF) for the structures are CCDC
915508e915514 (Table 3). A copy of the data can be obtained free of
charge from CCDC, 12 Union Road, Cambridge CB2 1EZ, UK or e-
mail: deposit@ccdc.cam.ac.uk are available. Supplementary data
associated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2013.07.052.
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